Measurement of gas phase nitric oxide (NO) concentrations in exhaled breath, originating from both the oral and nasal passages, can be useful in the diagnosis of several disease states (e.g., asthma) and in the assessment of the risk of frequent infections of the upper airways. Higher levels of NO exist in exhaled nasal breath vs. oral breath, and it is believed that these increased levels of NO originate from NO production in healthy sinus tissues (epithelial cells) that serve to prevent sinus and lung infections, owing to NO's potent antimicrobial/antibiofilm/antiviral activity. Hence, patients with lower levels of exhaled nasal NO are at risk for increased rates of infection and chronic rhinosinusitis (CRS). It is estimated that up to 13% of the US population suffers from CRS. Existing methods to accurately monitor gas phase NO that could aid in identifying patients prone to CRS are complex and costly (e.g., chemiluminescence and mass spectrometry) and not easily adapted for near patient testing. Available electrochemical NO sensors, especially amperometric devices, are relatively simple and inexpensive, but lack of selectivity for NO over carbon monoxide (CO) is problematic in applying such devices for reliable measurements of exhaled gas phase NO to monitor patients. Further, adapting the devices to a gas phase sensing mode with the low detection limits required to be clinically useful has been challenging. This exploratory project builds on a recent discovery that selectivity for NO over CO can be dramatically enhanced when oxide coatings are present on the surface of working electrodes employed to prepare amperometric NO sensors. Hence, this proposal aims to 1a) optimize the formation of oxide layers on the surface of the working electrodes of NO sensors based on conventional (inner working electrode) configurations (Shibuki) and a newer design in which the working electrode is deposited on a solid-electrolyte polymeric film (for both Pt and Au electrodes) by controlling pH and applied polarization potential; 1b) study the analytical performance (sensitivity and selectivity) of these more selective and sensitive NO sensors in detecting NO in flowing gas phase streams using microcontrollers to carefully control gas phase flow rates; and 2) test the most promising amperometric gas phase NO sensors derived from Aim 1 studies to detect NO in exhaled nasal breath collected from healthy human subjects and correlate levels of NO determined by the new gas phase sensors to values measured by the gold-standard chemiluminescence method. It is anticipated that the results of this exploratory study will provide the basis for creating advanced electrochemical NO sensors that will have wide utility in near patient testing of exhaled NO levels to help in diagnosing and treating patients with CRS or asthma.